Hepatocarcinogenesis in the Context of Strain Differences in Energy Metabolism Between Inbred Strains of Mice (C57BL/6J and C3H/He)
Liver neoplasia in mice is one of the most frequent tumor target tissue endpoints observed in 2-year carcinogenicity studies of the US National Toxicology Program (NTP). B6C3F1 mice are the hybrids of male C3H/He, which are highly sensitive (hepatomas in 7291% at 14 months), and C57B1/6J females, which exhibit a low susceptibility to spontaneous and chemically induced hepatocarcinogenesis (Heston, 1963; Drinkwater and Bennett, 1991; Dragani et al. 1995; Wastl et al. 1998). Thus, the validity of mouse liver tumor endpoint in assessing the potential hazards of chemical exposure to humans is a controversial issue, since tumor susceptibility varies even within inbred strains of mice. Therefore our studies aimed to elucidate strain specifities that may modulate tumor development to improve the assessment for the relevance of mouse liver tumor induction in toxicological testing of chemicals.
KeywordsObesity Sucrose Glycerol Cage Respiration
Unable to display preview. Download preview PDF.
- Berry, M. J., Grieco, D., Taylor, B. A., Maia, A. L., Kieffer, J. D., Beamer, W., Glover, E., Poland, A., and Larsen, P. R., 1993, Physiological and genetic analyses of inbred mouse strains with a type I iodothyronine 5’ deiodinase deficiency J Clin. Inve st. 92:1517–1528.PubMedCrossRefGoogle Scholar
- Chance, B., Sies, H., and Boveris, A., 1979, Hydroperoxide metabolism in mammalian organs, Physiol. Rev. 59:527–605.Google Scholar
- Chavin, K. D., Yang, S., Lin, H. Z., Chatham, J., Chacko, V. P., Hoek, J. B., Walajtys Rode, E., Rashid, A., Chen, C. H., Huang, C. C., Wu, T. C., Lane, M. D., and Diehl, A. M., 1999, Obesity induces expression of uncoupling protein-2 in hepatocytes and promotes liver ATP depletion, J Biol. Chem. 274:5692–5700.PubMedCrossRefGoogle Scholar
- Fleury, C., Neverova, M., Collins, S., Raimbault, S., Champigny, O., Levi Meyrueis, C., Bouillaud, F., Seldin, M. F., Survit, R. S., Ricquier, D., and Warden, C. H., 1997, Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia, Nat. Genet. 15:269–272.Google Scholar
- Heston, W. E., 1963, Genetics of neoplasia, in: Methodology in mammalian genetics (W. J. Burdette, ed.), Holden-Day, San Francisco, pp. 247–268.Google Scholar
- Porter, R. K., Joyce, O. J., Fanner, M. K., Heneghan, R, Tipton, K. F., Andrews, J. F., McBennett, S. M., Lund, M. D., Jensen, C. R, and Melia, H. P., 1999, Indirect measurement of mitochondrial proton leak and its application, Int. J. Obes. Relat. Metab. Disord 23 Suppl. 6:12–18.CrossRefGoogle Scholar
- Rashid, A., Wu, T. C., Huang, C. C., Chen, C. R, Lin, H. Z., Yang, S. Q., Lee, F. Y., Diehl, A. M., Gong, D. W., He, Y., and Reitman, M. L., 1999, Mitochondrial proteins that regulate apoptosis and necrosis are induced in mouse fatty liver. Genomic organization and regulation by dietary fat of the uncoupling protein 3 and 2 genes, Hepatology 29:1131–1138.PubMedCrossRefGoogle Scholar
- Staniek, K., and Nohl, R, 1999, H(2)O(2) detection from intact mitochondria as a measure for one-electron reduction of dioxygen requires a non-invasive assay system, Biochim. Biophys. Acta 1413:70–80.Google Scholar